Project Summary/Abstract Translation is essential for all biological processes including development, differentiation, growth, cell fitness and cellular adaptive responses to the external environment. Consequently, regulatory dysfunction in translation is associated with various human diseases such as metabolic disorders, neuronal degenerative diseases and cancer. Our long-term goal is to elucidate molecular mechanisms of translation and translational control in gene expression, and to understand how errors in this process are related to human disease. Towards this goal, the overall objective of the proposed research is to elucidate molecular mechanisms and interactions that enable RNA-binding protein Sbp1 to remodel and activate the 5' untranslated regions (5'UTRs) of mRNAs encoding eukaryotic initiation factor 4G (eIF4G). Four independent but complementary aims are proposed. Aim 1 pursues a molecular understanding of how Sbp1 influences the formation of intermediates in translation initiation of the eIF4G mRNAs. Aim 2 and 3 seek to understand the functions of individual domains of the Sbp1 in modulating protein- protein and protein-RNA interactions. Aim 4 is designed to reveal molecular architectures of several functional 5'UTR-protein complexes in translation initiation. These aims will be accomplished by using biochemical methods.